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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the detailed mechanism of reactive oxygen species (ROS) regulation is still unclear. This study examined the effect of high-salt diet on ROS production and expression of antioxidant enzymes in control and experimentally diabetic rats. Wistar fatty rats (WFR) as a type 2 diabetes mellitus model and Wistar lean rats (WLR) as a control were fed a normal-salt diet (NS) and high-salt diet (HS) from the age of 6 to 14 weeks. We then examined the blood pressure, urinary albumin excretion (UAE), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The expression of antioxidant enzymes including alpha-catalase (CAT), Cu-Zn superoxide dismutase (SOD), Mn SOD, and glutathione peroxidase (GPx) were analyzed in the glomeruli of the rats using Western blotting. The expression of NAD(P)H oxidase p47(phox) and NFkappaB p65 was evaluated using immunohistochemical staining. By 14 weeks of age, the WFR-HS group exhibited hypertension and markedly increased UAE. The level of 8-OHdG, a marker of oxidative damage, in the WFR-HS group was also higher than that in the WLR groups or WFR-NS group. The expression of alpha-CAT and Mn SOD proteins was significantly decreased in isolated glomeruli in the WFR-HS group. GPx and Cu-Zn SOD expression did not differ between the WFR and WLR groups. High expression of ROS and decreases in antioxidants were seen in the glomeruli of diabetic rats with hypertension, suggesting that oxidative stress may be involved in the development of DN.
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PMID:Hypertension aggravates glomerular dysfunction with oxidative stress in a rat model of diabetic nephropathy. 1733 48

The development of diabetic complications has usually been attributed to the nonenzymic glycation of tissue proteins. Only recently, however, have researchers examined the possible role on free radicals in the pathogenesis of diabetes. In the present study, glutathione (GSH) and major antioxidant enzyme levels in plasma of patients with type II diabetes mellitus were assessed both before and after 3 months of N-acetylcysteine (NAC) therapy. Thirty-two diabetic patients were examined as well as fifteen healthy controls. Before treatment with NAC, glutathione peroxidase (GPx), catalase (CAT), and (GSH) levels of diabetic patients and control subjects showed no significant differences, whereas glutathione S-transferase (GST) levels were higher in type II diabetic patients. Following 3 months of Following NAC supplementation, GSH, GST, and CAT levels were found to be similar to the levels before treatment. On the other hand, GPx activity was significantly lower compared with the values before treatment. According to this finding, NAC treatment could have a positive effect on GPx values in type II diabetic patients showing abnormally high values.
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PMID:The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. 1733 80

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.
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PMID:Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients. 1736 36

Diabetes mellitus has assumed epidemic proportions in most parts of the world, and it is a major source of morbidity in developed countries. In addition, in several instances, diabetes is associated with a variety of metabolic abnormalities, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and hyperglycemia. There is considerable evidence that hyperglycemia causes the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response by the endogenous antioxidants, such as vitamins C and E, catalase, glutathione, and superoxide dismutase, oxidative stress dominates, resulting in the activation of stress-sensitive intracellular signaling pathways. One of the major consequences is the generation of gene products that cause cellular damage and are ultimately responsible for the late complications of diabetes. The ability of antioxidants to protect against the effects of hyperglycemia in vitro, along with the clinical benefits often reported following antioxidant therapy, supports a causative role of oxidative stress in mediating and/or worsening these abnormalities. This review will focus on the critical assessment of the literature as it relates to the association between oxidative stress and diabetes, followed by the role of oxidative stress in the complications of type 2 diabetes mellitus. Finally, a review of the use of the antioxidant vitamin E will be provided in diabetic patients by assessing and evaluating some of the clinical trials in the literature.
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PMID:The use of vitamin E in type 2 diabetes mellitus. 1749 41

Reduced insulin sensitivity is characteristic of various pathological conditions such as type 2 diabetes mellitus and hypertension. Angiotensin II, acting through its angiotensin type 1 receptor, inhibits the actions of insulin in the vasculature which may lead to deleterious effects such as vascular inflammation, remodeling, endothelial dysfunction, and insulin resistance. In contrast, insulin normally exerts vasodilatory, antiinflammatory, and prosurvival actions. To explore the impact of angiotensin II on insulin signaling, NADPH oxidase-derived reactive oxygen species formation, vascular inflammation, apoptosis, and remodeling, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse renin transgene and exhibits elevated tissue angiotensin II levels. Compared with Sprague-Dawley controls, Ren2 aortas exhibited greater NADPH oxidase activity, reactive oxygen species levels, C-reactive protein, tumor necrosis factor-alpha expression, apoptosis, and wall thickness, which were significantly attenuated by in vivo treatment with angiotensin type 1 receptor blockade (valsartan) or the superoxide dismutase/catalase mimetic (tempol). There was substantially diminished Akt and endothelial NO synthase activation in Ren2 aortas in response to in vivo insulin stimulation, and this was significantly improved by in vivo treatment with valsartan or tempol. In vivo treatment with valsartan, but not tempol, significantly reduced blood pressure in Ren2 rats. Further, there was reduced insulin induced Akt activation and increased tumor necrosis factor-alpha levels in vascular smooth muscle cells from Ren2 and Sprague-Dawley rats treated with angiotensin II, abnormalities that were abrogated by angiotensin type 1 receptor blockade with valsartan or antioxidant N-acetylcysteine. Collectively, these data suggest that increased angiotensin type 1 receptor/NADPH oxidase activation/reactive oxygen species contribute to vascular insulin resistance, endothelial dysfunction, apoptosis, and inflammation.
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PMID:NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat. 1753 99

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and metformin on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin-nicotinamide induced type 2 diabeteic model was investigated. Succinic acid monoethyl ester was administered intraperitonially for 30 days to control and diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of EMS was compared with metformin, a reference drug. The levels of glucose, glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased significantly whereas the level of insulin and hemoglobin, as well as antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in EMS and metformin treated diabetic rats. The present study indicates that the EMS possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.
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PMID:Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetes. 1753 13

Oxidative stress is a putative mechanism leading to beta-cell damage in type 2 diabetes. We studied isolated human pancreatic islets from type 2 diabetic and non-diabetic subjects, matched for age and body mass index. Evidence of increased oxidative stress in diabetic islets was demonstrated by measuring nitrotyrosine concentration and by electron paramagnetic resonance. This was accompanied by reduced glucose-stimulated insulin secretion, as compared to non-diabetic islets (Stimulation Index, SI: 0.9 +/- 0.2 vs. 2.0 +/- 0.4, P<0.01), and by altered expression of insulin (approximately -60%), catalase (approximately +90%) and glutathione peroxidase (approximately +140%). When type 2 diabetic islets were pre-exposed for 24 h to the new antioxidant bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate di-hydrochloride, nitrotyrosine levels, glucose-stimulated insulin secretion (SI: 1.6+/-0.5) and gene expressions improved/normalized. These results support the concept that oxidative stress may play a role in type 2 diabetes beta-cell dysfunction; furthermore, it is proposed that therapy with antioxidants could be an interesting adjunctive pharmacological approach to the treatment of type 2 diabetes.
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PMID:Insulin secretion defects of human type 2 diabetic islets are corrected in vitro by a new reactive oxygen species scavenger. 1761 74

We investigated the possible involvement of thyroid hormones and lipid peroxidation in the antidiabetic potential of rosiglitazone (a peroxisome proliferator-activated receptors gamma-agonist) on corticosteroid-induced type 2 diabetes mellitus. Rosiglitazone was administered to dexamethasone-induced hyperglycaemic male mice and the alterations in serum concentrations of thyroid hormones insulin, total cholesterol, triglycerides and fasting glucose were studied. Simultaneously changes in lipid peroxidation, reduced glutathione (GSH) content, superoxide dismutase and catalase activities in renal and cardiac tissues (which are commonly affected in diabetes mellitus), were also investigated. Administration of dexamethasone (1.0 mg/kg/day intramuscularly for 28 days) caused hyperglycaemia with a parallel increase in serum insulin, total cholesterol, triglycerides and tissue lipid peroxidation with a decrease in serum levels of both the thyroid hormones (triiodothyronine, T(3) and thyroxine, T(4)) and in the activity of associated tissue antioxidants such as superoxide, catalase and glutathione. However, rosiglitazone administration (3.2 mg/kg/day orally for 21 days) along with an equivalent amount of dexamethasone reverted most of these changes, including a marked inhibition of tissue lipid peroxidation and an increase in the serum levels of both thyroid hormones. The present findings reveal that the test drug ameliorates corticosteroid-induced type 2 diabetes mellitus through an increase in serum thyroid hormone concentrations and inhibition in tissue lipid peroxidation.
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PMID:Amelioration of corticosteroid-induced type 2 diabetes mellitus by rosiglitazone is possibly mediated through stimulation of thyroid function and inhibition of tissue lipid peroxidation in mice. 1769 37

Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of aak-2, a homolog of AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired glycolysis. Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or "mitohormesis." Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements.
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PMID:Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. 1790 57

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (beta-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.
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PMID:Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. 1792 55


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